title: Lineage tracing and cell ablation identify a post-Aire-expressing thymic epithelial cell population.
abstract: Thymic epithelial cells in the medulla (mTECs) play a critical role in enforcing central tolerance through expression and presentation of tissue-specific antigens (TSAs) and deletion of autoreactive thymocytes. TSA expression requires autoimmune regulator (Aire), a transcriptional activator present in a subset of mTECs characterized by high CD80 and major histocompatibility complex II expression and a lack of potential for differentiation or proliferation. Here, using an Aire-DTR transgenic line, we show that short-term ablation specifically targets Aire(+) mTECs, which quickly undergo RANK-dependent recovery. Repeated ablation also affects Aire(-) mTECs, and using an inducible Aire-Cre fate-mapping system, we find that this results from the loss of a subset of mTECs that showed prior expression of Aire, maintains intermediate TSA expression, and preferentially migrates toward the center of the medulla. These results clearly identify a distinct stage of mTEC development and underscore the diversity of mTECs that play a key role in maintaining tolerance.
authors.affiliation: Diabetes Center, University of California, San Francisco, San Francisco, CA 94143-0540, USA.
authors.forename: Todd C
authors.initials: TC
authors.lastname: Metzger
authors.forename: Imran S
authors.initials: IS
authors.lastname: Khan
authors.forename: James M
authors.initials: JM
authors.lastname: Gardner
authors.forename: Maria L
authors.initials: ML
authors.lastname: Mouchess
authors.forename: Kellsey P
authors.initials: KP
authors.lastname: Johannes
authors.forename: Anna K
authors.initials: AK
authors.lastname: Krawisz
authors.forename: Katarzyna M
authors.initials: KM
authors.lastname: Skrzypczynska
authors.forename: Mark S
authors.initials: MS
authors.lastname: Anderson
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction; D060168:Thymocytes / Q000166:cytology* / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism*